文献类型：期刊文献

英文题名：Reduction and Suppression of Methemoglobin Loaded in the Polymeric Nanoparticles Intended for Blood Substitutes

作者：Zhang, Xiaolan[1];Liu, Changsheng[1];Yuan, Yuan[1];Shan, Xiaoqian[1];Sheng, Yan[1];Xu, Feng[1]

机构：[1]E China Univ Sci & Technol, Minist Educ, Engn Res Ctr Biomed Mat, Key Lab Ultrafine Mat, Shanghai 200237, Peoples R China

年份：2008

卷号：87B

期号：2

起止页码：354

外文期刊名：JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS

收录：;EI(收录号：20084511682359);WOS:【SCI-EXPANDED(收录号:WOS:000260355000007)】；

基金：Contract grant sponsor: National High Technology Research and Development Program of China (863 Program); contract grant number: 2004AA-302050Contract grant sponsor: Shanghai Nanotechnology Special Foundation; contract grant number: 0452nm022

语种：英文

外文关键词：methemoglobin; oxidation; reduction; suppression; double emulsion

摘要：Oxidation of hemoglobin (Hb) to nonfunctional methemoglobin (metHb) is a main challenge for the fabrication of an ideal Hb-based blood substitute. In this study, a novel nonenzymatic reduction and suppression route, combined with a fast prereduction, optimized double emulsion preparation, and a second sustaining postreduction, was developed to control the metHb in Hb-loaded nanoparticles (HbP) with porous microstructure to a desirable level. In the prereduction, the metHb in the raw Hb was effectively reduced from over 90% to 1.2% using sodium dithionite following gel filtration separation. During the preparation, higher the emulsion strength performed, higher was the extent of Hb oxidized. PEGylated polymer and addition of miscible solvent, such as acetonitrile, into the oil phase could pronouncedly suppress metHb formation. The resultant metHb level in HbP under the optimal fabrication was about 5.6%, which could be further reduced to 1.4% by the model reducing agents in human plasma with the help of superoxide dismutatse and catalase system, which are capable of sustaining postreduction. The oxygen dissociation curve of the HbP was close to that of native Hb, indicating that the oxygen-carrying ability of the Hb, despite initially losing this function due to the severe oxidation, recovered and retained well. The results achieved are promising for the fabrication of blood substitutes with controlled metHb level, which can fulfill the binding/delivering oxygen to tissues in vivo for future trials. (C) 2008 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 87B: 354-363, 2008